n-3 polyunsaturated fatty acids and cardiovascular diseases.Nordøy A: Department of Medicine, University of Tromsø, Norway; Marchioli R, Arnesen H, Videbaek JLipids 2001 36 Suppl:S127-9AbstractAn expert round table discussion on the relationship between intake of n-3 polyunsaturated fatty acids (PUFA) mainly of marine sources and coronary heart disease at the 34th Annual Scientific Meeting of European Society for Clinical Investigation came to the following conclusions: 1. Consumption of 1-2 fish meals/wk is associated with reduced coronary heart disease (CHD) mortality. 2. Patients who have experienced myocardial infarction have decreased risk of total, cardiovascular, coronary, and sudden death by drug treatment with 1 g/d of ethylesters of n-3 PUFA, mainly as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The effect is present irrespective of high or low traditional fish intake or simultaneous intake of other drugs for secondary CHD prevention. n-3 PUFA may also be given as fatty fish or triglyceride concentrates. 3. Patients who have experienced coronary artery bypass surgery with venous grafts may reduce graft occlusion rates by administration of 4 g/d of n-3 PUFA. 4. Patients with moderate hypertension may reduce blood pressure by administration of 4 g/d of n-3 PUFA.5. After heart transplantation, 4 g/d of n-3 PUFA may protect against development of hypertension. 6. Patients with dyslipidemia and or postprandial hyperlipemia may reduce their coronary risk profile by administration of 1-4 g/d of marine n-3 PUFA. The combination with statins seems to be a potent alternative in these patients. 7. There is growing evidence that daily intake of up to 1 energy% of nutrients from plant n-3 PUFA (alpha-linolenic acid) may decrease the risk for myocardial infarction and death in patients with CHD. This paper summarizes the conclusions of an expert panel on the relationship between n-3 PUFA and CHD. The objectives for the experts were to formulate scientifically sound conclusions on the effects of fish in the diet and the administration of marine n-3 PUFA, mainly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), and eventually of plant n-3 PUFA, alpha-linolenic acid (ALA, 18:3n-3), on primary and secondary prevention of CHD. Fish in the diet should be considered as part of a healthy diet low in saturated fats for everybody, whereas additional administration of n-3 PUFA concentrates could be given to specific groups of patients. This workshop was organized on the basis of questions sent to the participants beforehand, on brief introductions by the participants, and finally on discussion and analysis by a group of approximately 40 international scientists in the fields of nutrition, cardiology, epidemiology, lipidology, and thrombosis.

Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial.Stark KD: Department of Human Biology and Nutritional Sciences, University of Guelph, Canada; Park EJ, Maines VA, Holub BJAm J Clin Nutr 2000 Aug 72:389-94AbstractBACKGROUND: n-3 Fatty acid supplementation lowered serum triacylglycerol concentrations in studies in which most of the subjects were male. The effects of n-3 fatty acid supplementation in postmenopausal women receiving and not receiving hormone replacement therapy (HRT) have received little attention. OBJECTIVE: We sought to determine the effects of a fish-oil-derived n-3 fatty acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular disease in postmenopausal women receiving and not receiving HRT, with an emphasis on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL cholesterol. DESIGN: Postmenopausal women (n = 36) were grouped according to exogenous hormone use and were randomly allocated to receive 8 capsules/d of either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic acid (DHA) daily. Serum lipids and the fatty acid composition of serum phospholipids were determined on days 0 and 28. RESULTS: Supplementation with n-3 fatty acids was associated with 26% lower serum triacylglycerol concentrations (P < 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol (P < 0.01), and markedly greater EPA and DHA concentrations in serum phospholipids (P < 0.05). CONCLUSIONS: These results show that supplementation with a fish-oil-derived concentrate can favorably influence selected cardiovascular disease risk factors, particularly by achieving marked reductions in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in postmenopausal women receiving and not receiving HRT. This approach could potentially reduce the risk of coronary heart disease by 27% in postmenopausal women.

Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women.Sanchez-Muniz FJ: Departmento de Nutricion y Bromatologia I, Facultad de Farmacia, Universidad Complutense, Madrid, Spain; Bastida S, Viejo JM, Terpstra AHEur J Nutr 1999 Feb 38:20-7AbstractIn order to investigate the effect of a short-term application of marine n-3 polyunsaturated fatty acids on the composition of serum very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), nine women aged 29 +/- 4.2 years, following a diet with a SFA/MUFA/PUFA profile of 2.4/3/1, received supplements of six capsules daily, each capsule containing 0.137 g of n-3 fatty acids (14.5% eicosapentaenoic acid (EPA) and 8.9% docosahexaenoic acid (DHA)) for 10 d. Food consumption, assessed during two 10-days periods indicates that percentage contribution of SFA, MUFA, and PUFA to the daily energy intake did not change through the fish-oil supplementation period, but the daily consumption of n-3 fatty acids increased 2.3 times. N-3 fatty supplementation increased EPA and DHA percentages in serum phospholipids, but failed to decrease (p > 0.05) the cholesterol and triglyceride concentration in serum LDL and HDL, although it did so in VLDL. In contrast, the lipoprotein-phospholipid and lipoprotein-protein concentrations were markedly affected, mainly in LDL and HDL (at least p < 0.01). HDL and VLDL compositions were not affected but the total mass (lipid + protein in mg/dl) concentration of these lipoproteins significantly decreased (p < 0.05), suggesting a lower number of these particles in circulating blood after the n-3 treatment. The LDL-cholesterol/LDL-apolipoprotein B ratio increased (p < 0.01) reflecting a probable increase in LDL size. Following fish oil supplementation, LDL particles contained a significantly lower amount of phospholipids, which also suggests changes in the surface/core ratio of the average LDL. Changes in serum lipoprotein lipids did not significantly correlate with any dietary change other than the n-3 fatty acid increase. The results indicate that a 10-day application of a small supplement of n-3 change the LDL composition leading to less atherogenic LDL particles with lower phospholipid and apolipoprotein (Apo) B concentrations.

The effect of n-3 fatty acid administration on selected indicators of cardiovascular disease risk in patients with type 2 diabetes mellitus.Habán P: Klinické oddelenie Výskumného ústavu výzivy v Bratislave; Simoncic R, Klvanová I, Ozdín L, Zideková EBratisl Lek Listy 1998 Jan 99:37-42AbstractBACKGROUND: Serum triacylglycerols (TG), VLDL, HDL, fatty acid and eicosanoid spectrum are among the factors determining the risk of cardiovascular complications in NIDDM. N-3 polyunsaturated fatty acids (PUFA) are expected to have beneficial effects on these factors. In NIDDM patients there have however been previously reported (late 1980s) some adverse effects. OBJECTIVES: Our aim was to verify the effects of n-3 PUFA in NIDDM patients using relatively low dosage. METHODS: The investigated group included 21 NIDDM patients with dyslipoproteinemia type IV. The patients were treated for 28 days with 1.7 g EPA (eicosapentaenoic acid) + 1.15 g DHA (docosahexaenoic acid)/day (10 capsules/day of MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the BIO-LACHEMA kits, the fatty acid spectrum in phospholipids was determined by gas chromatography and prostanoids (after their separation) were measured by RIA methods. MAIN RESULTS AND CONCLUSIONS: After the MAXEPA treatment there has been a strong decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels, accompanied by a significant increase in HDL (p < 0.02). The final-to-baseline TG ratio in individual patients negatively correlated with the relative percentage of EPA in phospholipids after the treatment (p < 0.03; r = -0.474). There was no significant change in serum total cholesterol, fasting glycaemia and glycosylated hemoglobin. There was a slight, but statistically already significant (p < 0.05), rise in LDL. The relative percentage of EPA, docosapentaenoic acid and DHA in serum phospholipids increased sharply (p < 0.001, p < 0.001, p < 0.001). The increase of n-3 PUFA in individual patients was linked with the decrease in n-6 PUFA (p < 0.001; r = -0.686). The spectrum of the latter has changed also very markedly. The prostacyclin PGI2-to-thromboxane TxA2 ratio increased significantly (p < 0.001). Beneficial effects of n-3 fatty acids have prevailed and this kind of treatment seems very encouraging also in NIDDM patients. The results are logically compatible with other authors' results pattern formed in 1990s. A slight rise in serum LDL needs a more detailed discussion since only its phenotype B ("small dense LDL particles") has been recently found to be atherogenic. (Tab. 2, Fig. 5, Ref. 15.)

Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women.Laidlaw M: Department of Human Biology and Nutritional Sciences, University of Guelph, Canada; Holub BJAm J Clin Nutr 2003 Jan 77:37-42AbstractBACKGROUND: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention. OBJECTIVE: The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids. DESIGN: Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28. RESULTS: Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups. CONCLUSIONS: A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction.

The effect of omega-3 fatty acids on risk factors for cardiovascular diseases.Yam D: Weizmann Institute of Science, Givatayim, Israel; Bott-Kanner G, Genin I, Shinitzky M, Klainman EHarefuah 2001 Dec 140:1156-8, 1230AbstractCardiovascular disease (CVD) is associated with dyslipidemia and frequently with insulin resistance, both of which are in general no alleviated by antilipidemic drugs. Our objective was to examine whether a dietary supplement containing omega-3 fatty acids (n-3 FA) can reduce the levels of serum lipids, fasting insulin and glucose in documented CVD patients treated by statins or bezafibrates. In a double-blind placebo-controlled trial of parallel design, 52 patients, age 69.2 years +/- 3.6 treated by antilipidemic drugs, were randomly assigned to receive daily 7 gr of a dietary concentrated supplement containing 67% n-3 FA (185 mg EPA and 465 mg/g DHA) in a form of spread (Yamega Ltd, Israel) or olive oil spread (placebo) and recommended to reduce the consumption of omega-6 fatty acids for 12 weeks. The average values +/- SD before and after dietary supplementations were compared. RESULTS: 44 patients (23 in the n-3 FA group) completed the study. In the n-3FA group we observed a significant decrease (p < 0.05) of total cholesterol (12.2%), LDL-cholesterol (16.8%), triglycerides (36.1%), insulin in hyperinsulinemic subjects (> 20 microunits/ml) (34.9%), and no significant changes in HDL-cholesterol and glucose. No hyperglycemia was detected. In the olive oil group we observed a significant decrease (p < 0.05) in the LDL-cholesterol values of 15.5% and no significant changes in the other parameters. No side effects were reported during the study in any of the participants. Our findings demonstrate that the incorporation of the dietary supplement containing EPA and DHA omega-3 fatty acids reduces significantly the above risk factors for CVD.

Study of the effects of dietary fish intake on serum lipids and lipoproteins in two populations with different dietary habits.Torres IC: Departamento de Quamica, Universidade da Madeira, Funchal, Portugal; Mira L, Ornelas CP, Melim ABr J Nutr 2000 Apr 83:371-9AbstractIncreased concentrations of n-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (20:5; EPA) and docosahexaenoic acid (22:6; DHA), have been shown to be beneficial in coronary artery disease (CAD). In the present study, the relationships between fish intake and concentrations of serum EPA and DHA and the effects of these fatty acids on serum lipids and lipoproteins were investigated. Two groups of men, one living in a fishing village and the other in a farming village, participated in this study. The daily fish consumption was ten times greater in the fishing village group than in the rural village group and the mortality from IHD in the rural village was four times higher. Serum concentrations of EPA and DHA were significantly higher in the fishing village group (P < 0.001). In this group, the serum concentration of arachidonic acid (20:4; AA), was significantly lower (P < 0.001), and the ratio EPA:AA was twice that of the rural village (P < 0.001). Moreover, in the fishing village group, the serum triacylglycerol and total cholesterol levels were significantly lower than those observed in the rural village (P < 0.01 and P < 0.05 respectively). In the fishing village group the serum LDL-cholesterol concentration was also lower, although the difference was not significant. Our results reinforce the hypothesis that a high intake of n-3 PUFA provides protection against CAD.

Habitual fish consumption, plasma phospholipid fatty acids, and serum lipids: the Tromsø study.Bønaa KH: Institute of Community Medicine, University of Tromsø, Norway; Bjerve KS, Nordøy AAm J Clin Nutr 1992 Jun 55:1126-34AbstractWe examined the cross-sectional relationships between the frequency of habitual fish consumption, plasma phospholipid fatty acids, and serum lipids and lipoproteins in 152 men and women. There was a significant association between fish consumption starting from 1 dish/wk and plasma n-3, n-6, and n-9 fatty acids. Plasma eicosapentaenoic acid (EPA; 20: 5n-3) reflected fish consumption to a greater extent than did docosahexaenoic acid (DHA;22:6n-3). Triglycerides decreased (P less than 0.05) with fish consumption. In multivariate analysis in which anthropometric and lifestyle factors were controlled for, EPA correlated inversely with triglycerides (P less than 0.05) and positively with high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I (both P less than 0.001). In contrast, DHA did not correlate with triglycerides and showed negative associations to HDL cholesterol and apolipoprotein A-I (both P less than 0.001). Platelet phospholipid EPA, but not DHA, was associated with lower triglyceride and higher HDL-cholesterol concentrations (both P less than 0.05). This study suggests that long-term intake of small amounts of fish has biological effects, and that EPA and DHA have divergent relations with lipoprotein metabolism.

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.Nilsen DW: Dept. of Medicine, University of Tromsö, Norway; Dalaker K, Nordaa A, OsThromb Haemost 1991 Aug 66:195-201Abstract Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up.TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention